Androgens and breast cancer

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Androgens and breast cancer

We have recently demonstrated that physiological levels of androgens exert direct and potent inhibitory effects on the growth of human breast cancer ZR-75-1 cells in vivo in nude mice as well as in vitro under both basal and estrogen-stimulated conditions. The inhibitory effect of androgens has also been confirmed on the growth of dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat. Such observations are in close agreement with the clinical data showing that androgens and the androgenic compound medroxyprogesterone acetate (MPA) have beneficial effects in breast cancer in women comparable to other endocrine therapies, including tamoxifen. Although the inhibitory action of androgens on cell proliferation in estrogen-induced ZR-75-1 cells results, in part, from their suppressive effect on expression of the estrogen receptor, the androgens also exert a direct inhibitory effect independent of estrogens. Androgens cause a global slowing effect on the duration of the cell cycle. These observations support clinical data showing that androgenic compounds induce an objective remission after failure of antiestrogen therapy as well as those indicating that the antiproliferative action of androgens is additive to that of antiestrogens. We have also recently demonstrated in ZR-75-1 human breast cancer cells the antagonism between androgens and estrogens on the expression of GCDFP-15 and GCDFP-24 which are two major proteins secreted in human gross cystic disease fluid. The effects of androgens and estrogens as well as those of progestins and glucocorticoids on GCDFP-15 and GCDFP-24 mRNA levels and secretion are opposite to those induced by the same steroids on cell growth in ZR-75-1 cells.

Supporting students with learning disabilities to explore linear relationships using online learning objects

The study of linear relationships is foundational for mathematics teaching and learning. However, students’ abilities connect different representations of linear relationships have proven to be challenging. In response, a computer-based instructional sequence was designed to support students’ understanding of the connections among representations. In this paper we report on the affordances of this dynamic mode of representation specifically for students with learning disabilities. We outline four results identified by teachers as they implemented the online lessons.

Heritage

This article examines the concepts, definitions, policies, and practices of heritage in a contemporary context. Within recent years, there have been significant shifts in our understandings and applications of heritage concepts and policies in the modern world. ‘Heritage’ emerged as a buzz word in international policy arenas in the 1980s and early 1990s, and has since weathered the vagaries of turbulent definitional and governance–nomenclature storms, as traditional debates about ‘what it is and what it is not’ reverberate around academia and state agencies alike. Policy and funding structures for heritage are determined by the classifications used to define them in various countries. Typically, reference is made to ‘built heritage’, ‘natural heritage’, and ‘intangible heritage’, loosely reflecting buildings, landscapes, and culture. Aspects of heritage are used by the cultural and tourism industries to add economic value, through heritage tourism sites, museums, and other activities. The cultural tourism product is often anchored around notions of heritage, and in postmodern, post-tourist societies, boundaries between culture, (travel) space, and identities are increasingly blurred. Issues of authenticity become important in the representation of heritage, and questions are asked about the validity of nostalgia versus realism. The role of heritage is examined in the context of identity formulation at individual and nation-state levels, and the political aspects of this are also discussed. Finally, heritage conservation is assessed through an examination of UNESCO’s World Heritage Site listing and protection strategy. In a changing world, new constructs of heritage, identity, authenticity, and representation will continue to emerge as meanings are constantly renegotiated over time and space.

Formalised peer mentoring pilot evaluation

Over the past ten years, mentoring of children and young people has become an increasingly important feature of social policy in the UK. This has been mirrored in the rapid growth in the number of mentoring schemes operating. However, it is widely acknowledged that no one single definition or model of mentoring exists; rather there are a number of different models providing support to young people in a range of settings. This research was undertaken during the autumn term of 2006 and the summer term of 2007. The methodology comprised an analysis of mentoring models in the 180 participating schools; questionnaires sent to all co-ordinators and to mentors/proteges in 40 schools; interviews with co-ordinators, pupils and support agents in 8 case study schools. Includes: •Introduction •Evaluation methodology •Analysis of school pilot application forms •Evaluation results •Conclusions •Recommendations •Bibliography •Appendices

Psychology and interventions for pupils at risk of underachievement and school exclusion: the year 10 effect

Findings are presented from a longitudinal study of over 1,500 adolescents. Some were engaged in interventions aimed at reducing social disaffection. Participants completed measures of social-identification, academic self-concept and motivation, and social, emotional and behavioural difficulties. Consistent with our previous research, developmental trends in identity and self-concept were found - adolescents became more negative about some school-based factors and more positive about aspects of identity. Trends were less clear in the 120 adolescents receiving interventions. Findings demonstrate the importance of psychology in work with young people. [Source: (2008) 'Invited Address, IUPsyS Invited Symposium, Invited Symposium, Symposium, Paper Session, Poster Session', International Journal of Psychology, 43:3, 348 - 527]

Peat, pine stumps and people: interactions behind climate, vegetation change and human activity in wetland archaeology at Loch Farlary, Northern Scotland

First paragraph: In 1993, a peat-cutter, Bruce Field, working on the blanket peat bank he rented from the Sutherland Estate by Loch Farlary, above Golspie in Sutherland (fig 1), reported to Scottish Natural Heritage and Historic Scotland several pieces of pine wood bearing axe marks. Their depth in the peat suggested the cut marks to be prehistoric. This paper summarizes the work undertaken to understand the age and archaeological significance of this find (see also Tipping et al 2001 in press). The pine trees were initially thought to be part of a population that flourished briefly across northern Scotland in the middle of the Holocene period from c 4800 cal BP (Huntley, Daniell & Allen 1997). The subsequent collapse across northernmost Scotland of this population, the pine decline, at around 4200-4000 cal BP is unexplained: climate change has been widely assumed (Dubois & Ferguson 1985; Bridge, Haggart & Lowe 1990; Gear & Huntley 1991) but anthropogenic activity has not been disproved (Birks 1975; Bennett 1995). It was hypothesized that the Farlary find would allow for the first time the direct link between human woodland clearance and the Early Bronze Age pine decline.

Fact, fiction and nostalgia: an assessment of heritage interpretation at living museums

This paper aims to explore and discuss the role of nostalgia (a concept that is inherently grounded within a psychological framework) in heritage interpretation from both provider and consumer perspectives. Whilst many cultural practitioners recognise the relationship between sentimentality and authenticity, particularly within a folk-heritage context, few have sought to examine the effect this has on the visitor experience. This paper questions visitors’ ability to objectively assess objects and experiences at heritage sites, and the role of practitioners in presenting often blurred views of social history that may sometimes negate historical fact. Drawing on case study research at two UK living museums, Blists Hill Victorian Town in Shropshire, England, and the Big Pit: National Coal Museum in Wales, notions of reminiscence, authenticity, myth and intangibility are considered within the framework of the interpretive experience. Findings suggest that the visitor experience is inherently subjective, highly individual and that the concept of intangibility is integral to an understanding of the nostalgia-authenticity debate.

An evaluation of the implementation of hand held health records with adults with learning disabilities: a cluster randomized controlled trial

Background: Personal health records were implemented with adults with learning disabilities (AWLD) to try to improve their health-care. Materials and Method: Forty GP practices were randomized to the Personal Health Profile (PHP) implementation or control group. Two hundred and one AWLD were interviewed at baseline and 163 followed up after 12 months intervention (PHP group). AWLD and carers of AWLD were employed as research interviewers. AWLD were full research participants. Results: Annual consultation rates in the intervention and control groups at baseline were low (2.3 and 2.6 visits respectively). A slightly greater increase occurred over the year in the intervention group 0.6 ()0.4 to 1.6) visits ⁄ year compared with controls. AWLD in PHP group reported more health problems at follow-up 0.9 (0.0 to 1.8). AWLD liked their PHP (92%) but only 63% AWLD and 55% carers reported PHP usage. Carers had high turnover (34%). Conclusions: No significant outcomes were achieved by the intervention.

Sequence variation in the CHAT locus shows no association with late-onset Alzheimer's disease

There is substantial evidence for a susceptibility gene for late-onset Alzheimer's disease (AD) on chromosome 10. One of the characteristic features of AD is the degeneration and dysfunction of the cholinergic system. The genes encoding choline acetyltransferase (ChAT) and its vesicular transporter (VAChT), CHAT and SLC18A3 respectively, map to the linked region of chromosome 10 and are therefore both positional and obvious functional candidate genes for late-onset AD. We have screened both genes for sequence variants and investigated each for association with late-onset AD in up to 500 late-onset AD cases and 500 control DNAs collected in the UK. We detected a total of 17 sequence variants. Of these, 14 were in CHAT, comprising three non-synonymous variants (D7N in the S exon, A120T in exon 5 and L243F in exon 8), one synonymous change (H547H), nine single-nucleotide polymorphisms in intronic, untranslated or promoter regions, and a variable number of tandem repeats in intron 7. Three non-coding SNPs were detected in SLC18A3. None demonstrated any reproducible association with late-onset AD in our samples. Levels of linkage disequilibrium were generally low across the CHAT locus but two of the coding variants, D7N and A120T, proved to be in complete linkage disequilibrium.